Institute of Human Genetics, Jena University Hospital, Friedrich Schiller University, Jena, Germany.
Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, Croatia.
Cytogenet Genome Res. 2021;161(1-2):82-92. doi: 10.1159/000513174. Epub 2021 Feb 17.
Melanoma is considered to be one of the most aggressive human tumors. Thus, early molecular diagnosis with risk factor stratification could be an efficacious strategy to increase the survival rates in affected patients. Murine cell lines B16-F1, B16-4A5, and S91 clone M3 are the ones most commonly applied in melanoma research. However, genetic peculiarities of these 3 cell lines have not been studied in detail before. Here, we closed this gap by molecular cytogenetic and array-comparative genomic hybridization studies and the translation of the characterized imbalances into the human genome. This study revealed severely rearranged karyotypes with in parts similar imbalances for all 3 cell lines. Interestingly, they involve genes known to play major roles in human melanoma. These are specifically the oncogenes and tumor suppressor genes, being associated with aggressive forms of melanoma. B16-F1, B16-4A5, and S91 clone M3 revealed aberrations which were similarly observed in human eye and skin but not in human uveal melanoma. Thus, they can be considered as model systems for advanced eye and skin melanoma.
黑色素瘤被认为是最具侵袭性的人类肿瘤之一。因此,早期进行分子诊断并进行风险因素分层可能是提高患者生存率的有效策略。B16-F1、B16-4A5 和 S91 clone M3 这三种鼠源细胞系是黑色素瘤研究中最常用的细胞系。然而,这些细胞系的遗传特征在之前尚未得到详细研究。在这里,我们通过分子细胞遗传学和 array-comparative 基因组杂交研究以及将特征性失衡转化为人类基因组来填补这一空白。这项研究揭示了所有三种细胞系的染色体组型严重重排,部分存在相似的失衡。有趣的是,它们涉及已知在人类黑色素瘤中起主要作用的基因。这些基因包括癌基因和肿瘤抑制基因,与侵袭性黑色素瘤有关。B16-F1、B16-4A5 和 S91 clone M3 显示出与人类眼部和皮肤中观察到的相似的异常,但在人眼黑色素瘤中未观察到。因此,它们可以被认为是晚期眼部和皮肤黑色素瘤的模型系统。